Cited by 500Gut microbiota and healthMicrobial Natural Products and BiosynthesisGastrointestinal motility and disorders

The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.

Commensal bacteria make GPCR ligands that mimic human signalling molecules

Open access

Cohen, Louis J., Esterhazy, Daria, Kim, Seong-Hwan, Lemetre, Christophe, Aguilar, Rhiannon R., Gordon, Emma A., Pickard, Amanda J., Cross, Justin R., Emiliano, Ana B., Han, Sun M., Chu, John, Vila-Farres, Xavier, Kaplitt, Jeremy, Rogoz, Aneta, Calle, Paula Y., Hunter, Craig, Bitok, J. Kipchirchir, Brady, Sean F.·2017·Nature

DOI 10.1038/nature23874PMC PMC5777231

Open this paper in CoChat — free account

Abstract

Commensal bacteria are believed to have important roles in human health. The mechanisms by which they affect mammalian physiology remain poorly understood, but bacterial metabolites are likely to be key components of host interactions. Here we use bioinformatics and synthetic biology to mine the human microbiota for N-acyl amides that interact with G-protein-coupled receptors (GPCRs). We found that N-acyl amide synthase genes are enriched in gastrointestinal bacteria and the lipids that they encode interact with GPCRs that regulate gastrointestinal tract physiology. Mouse and cell-based models demonstrate that commensal GPR119 agonists regulate metabolic hormones and glucose homeostasis as efficiently as human ligands, although future studies are needed to define their potential physiological role in humans. Our results suggest that chemical mimicry of eukaryotic signalling molecules may be common among commensal bacteria and that manipulation of microbiota genes encoding metabolites that elicit host cellular responses represents a possible small-molecule therapeutic modality (microbiome-biosynthetic gene therapy).

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1038/nature23874

Cites

45 of 45 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Structure, function and diversity of the healthy human microbiome
The Human Microbiome Project Consortium (2012) · Nature · doi:10.1038/nature11234 · Cited by 11,726
Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-α
Fu, J., Gaetani, S., Oveisi, F., Verme, J., Serrano, A., de Fonseca, F. D., Rosengarth, A., Luecke, H., Giacomo, B. D., Tarzia, G., et al. (2003) · Nature · doi:10.1038/nature01921 · Cited by 1,113
Relating the metatranscriptome and metagenome of the human gut
Franzosa, E. A., Morgan, X. C., Segata, N., Waldron, L., Reyes, J. A., Earl, A. M., Giannoukos, G., Boylan, M. R., Ciulla, D., Gevers, D., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1319284111 · Cited by 731
Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents
Overton, H. A., Babbs, A. J., Doel, S. M., Fyfe, M. C. T., Gardner, L. S., Griffin, G., Jackson, H. C., Procter, M. J., Rasamison, C. M., Tang‐Christensen, M., et al. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.004 · Cited by 670
The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut
Kabashima, K., Saji, T., Murata, T., Nagamachi, M., Matsuoka, T., Segi‐Nishida, E., Tsuboi, K., Sugimoto, Y., Kobayashi, T., Miyachi, Y., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14459 · Cited by 443
Modulating the endocannabinoid system in human health and disease – successes and failures
Pacher, P., & Kunos, G. (2013) · FEBS Journal · doi:10.1111/febs.12260 · Cited by 418
The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut
Kabashima, K., Saji, T., Murata, T., Nagamachi, M., Matsuoka, T., Segi‐Nishida, E., Tsuboi, K., Sugimoto, Y., Kobayashi, T., Miyachi, Y., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0214459 · Cited by 418
GPR119 Is Essential for Oleoylethanolamide-Induced Glucagon-Like Peptide-1 Secretion From the Intestinal Enteroendocrine L-Cell
Lauffer, L. M., Iakoubov, R., & Brubaker, P. L. (2009) · Diabetes · doi:10.2337/db08-1237 · Cited by 405
A Role for Intestinal Endocrine Cell-Expressed G Protein-Coupled Receptor 119 in Glycemic Control by Enhancing Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Peptide Release
Chu, Z., Carroll, C., Alfonso, J., Gutierrez, V., He, H., Lucman, A., Pedraza, M., Mondala, H., Gao, H., Bagnol, D., et al. (2008) · Endocrinology · doi:10.1210/en.2007-0966 · Cited by 387
Programming a Human Commensal Bacterium, Bacteroides thetaiotaomicron, to Sense and Respond to Stimuli in the Murine Gut Microbiota
Mimee, M., Tucker, A. C., Voigt, C. A., & Lu, T. K. (2015) · Cell Systems · doi:10.1016/j.cels.2015.06.001 · Cited by 387

Show all 45 references

Sorted by citations

Items 201–300 of 499

G protein-coupled receptors: A target for microbial metabolites and a mechanistic link to microbiome-immune-brain interactions
Aleti, G., Troyer, E. A., & Hong, S. (2023) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2023.100671 · Cited by 30
Research advances in the diagnosis and treatment of MASLD/MASH
Wang, D., Miao, J., Zhang, L., & Zhang, L. (2024) · Annals of Medicine · doi:10.1080/07853890.2024.2445780 · Cited by 35
Implications of the microbiome in the development and treatment of pancreatic cancer: Thinking outside of the box by looking inside the gut
Yu, Q., Jobin, C., & Thomas, R. M. (2021) · Neoplasia · doi:10.1016/j.neo.2020.12.008 · Cited by 31
“[30] Cohen LJ , Esterhazy D , Kim S-H , Lemetre C , Aguilar RR , Gordon EA , Pickard AJ , Cross JR , Emiliano AB , Han SM , et al.”
Background
The Microbiota–Gut–Brain Axis: Gut Microbiota Modulates Conspecific Aggression in Diversely Selected Laying Hens
Hu, J., Johnson, T. A., Zhang, H., & Cheng, H. W. (2022) · Microorganisms · doi:10.3390/microorganisms10061081 · Cited by 29
Postprandial gut microbiota-driven choline metabolism links dietary cues to adipose tissue dysfunction
Schugar, R. C., Willard, B. B., Wang, Z., & Brown, J. M. (2017) · Adipocyte · doi:10.1080/21623945.2017.1398295 · Cited by 31
Human gut microbiota and their production of endocannabinoid-like mediators are directly affected by a dietary oil
Roussel, C., Sola, M., Lessard‐Lord, J., Nallabelli, N., Généreux, P., Cavestri, C., Wallen, O. A., Villano, R., Raymond, F., Flamand, N., et al. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2335879 · Cited by 28
“26,59 Our observation of a significant enrichment of Bacteroides in both clusters following BO led us to investigate the production of this metabolite, which was indeed increased in L_AC and, particularly, L_IL.”
Background
Probiotic-induced enrichment of Adlercreutzia equolifaciens increases gut microbiome wellness index and maps to lower host blood glucose levels
Zhang, Z., Yang, Z., Lin, S., Jiang, S., Zhou, X., Li, J., Lü, W., & Zhang, J. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2520407 · Cited by 31
“Using NCBI database alignment, we identified that A. equolifaciens contains genes for acyltransferase family proteins and aminotrans-ferases, which may be involved in the biosynthesis of palmitoyl serinol 45 (Figure 4(d)).”
Concurrent and long-term associations between the endometrial microbiota and endometrial transcriptome in postpartum dairy cows
Moore, S. G., Ericsson, A. C., Behura, S. K., Lamberson, W. R., Evans, T. J., McCabe, M. S., Poock, S. E., & Lucy, M. C. (2019) · BMC Genomics · doi:10.1186/s12864-019-5797-8 · Cited by 28
Microbial Therapeutics in Neurocognitive and Psychiatric Disorders
Alagiakrishnan, K., & Halverson, T. (2021) · Journal of Clinical Medicine Research · doi:10.14740/jocmr4575 · Cited by 29
Lipidomic Analysis Reveals Differences in Bacteroides Species Driven Largely by Plasmalogens, Glycerophosphoinositols and Certain Sphingolipids
Ryan, E., Pastor, B. G., Gethings, L. A., Clarke, D. J., & Joyce, S. A. (2023) · Metabolites · doi:10.3390/metabo13030360 · Cited by 28
Microbiota, natural products, and human health: exploring interactions for therapeutic insights
Qadri, H., Shah, A. H., Almilaibary, A., & Mir, M. A. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1371312 · Cited by 31
“Subsequent research (Cohen et al., 2017) expanded the repertoire of N-acyl amides from the human microbiome, revealing structural similarities to endogenous GPCR ligands.”
Background
Identification of a Quorum Sensing-Dependent Communication Pathway Mediating Bacteria-Gut-Brain Cross Talk
Uhlig, F., Grundy, L., Garcia‐Caraballo, S., Brierley, S. M., Foster, S. J., & Grundy, D. (2020) · iScience · doi:10.1016/j.isci.2020.101695 · Cited by 26
The microbiota–gut–brain axis: A novel nutritional therapeutic target for growth retardation
Qi, M., Tan, B., Wang, J., Liao, S., Deng, Y., Ji, P., Song, T., Zha, A., & Yin, Y. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1879004 · Cited by 27
The human periconceptional maternal-embryonic space in health and disease
Moreno, I., Capalbo, A., Mas, A., Garrido‐Gómez, T., Rosón, B., Poli, M., Dimitriadis, E., Santamaría, X., Vilella, F., & Simón, C. (2023) · Physiological Reviews · doi:10.1152/physrev.00050.2021 · Cited by 32
Uropathogenic Escherichia coli invades bladder epithelial cells by activating kinase networks in host cells
Kim, W.-J., Shea, A. E., Kim, J. H., & Daaka, Y. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.003499 · Cited by 25
“It is equally plausible thatUPECCMcontainsGPCR ligand agonists (41, 42) that promote a GPCR3 EGFR transactivation signal.”
Background
Chemical Reporters for Exploring Microbiology and Microbiota Mechanisms
Zhang, Z. J., Wang, Y., Yang, X., & Hang, H. C. (2019) · ChemBioChem · doi:10.1002/cbic.201900535 · Cited by 26
Microbial metabolite-receptor interactions in the gut microbiome
Chang, P. V. (2024) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2024.102539 · Cited by 31
Microbiota as Drivers and as Therapeutic Targets in Ocular and Tissue Specific Autoimmunity
Salvador, R., Zhang, A., Horai, R., & Caspi, R. R. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.606751 · Cited by 25
“Furthermore, small signaling molecules and metabolites are also found to have the potential of being convergent between microbial and human sources, and there have been ongoing efforts to mine the human metagenomes for these candidate small molecules (Cohen et al., 2017).”
Background
Multiomics signatures of type 1 diabetes with and without albuminuria
Clos‐Garcia, M., Ahluwalia, T. S., Winther, S. A., Henriksen, P., Ali, M., Fan, Y., Stankevič, E., Lyu, L., Vogt, J. K., Hansen, T. F., et al. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1015557 · Cited by 25
“Bacteria-derived sphingolipids have been reported to act as ligands for G protein-coupled receptors (33), including those found in the intestinal epithelium (34, 35).”
Background
Analysis of the oral microbiome during hormonal cycle and its alterations in menopausal women: the “AMICA” project
Tramice, A., Paris, D., Manca, A., Agudelo, F. A. G., Petrosino, S., Siracusa, L., Carbone, M., Melck, D. J., Raymond, F., & Piscitelli, F. (2022) · Scientific Reports · doi:10.1038/s41598-022-26528-w · Cited by 25
Cooperative enzymatic control of N-acyl amino acids by PM20D1 and FAAH
Kim, J. T., Terrell, S. M., Li, V. L., Wei, W., Fischer, C. R., & Long, J. Z. (2020) · eLife · doi:10.7554/elife.55211 · Cited by 24
“Potential candidate pathways include additional amidase enzymes on other N-acyl amino acid substrates, enzymes that catalyze the conjugation of fatty acid CoAs with amino acids, or non-mammalian sources (Brady et al., 2004; Cohen et al., 2017; Jeffries et al., 2016; Van Wagoner and Clardy, 2006).”
Background
Role of microbial metabolites in cardiovascular and human health
Singh, A. S. C. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-822238-6.00009-1 · Cited by 24
Intestinal GPR119 activation by microbiota-derived metabolites impacts feeding behavior and energy metabolism
Igarashi, M., Hayakawa, T., Tanabe, H., Watanabe, K., Nishida, A., & Kimura, I. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101649 · Cited by 24
“Collectively, intestinal GPR119 senses OEA or other ligands, such as N-acyl amides, in the intestinal contents or tissues after meals [18], which induces signals that regulate physiological responses such as feeding behavior.”
Background
Food System Transformation and Gut Microbiota Transition: Evidence on Advancing Obesity, Cardiovascular Diseases, and Cancers—A Narrative Review
Elechi, J. O. G., Sirianni, R., Conforti, F. L., Cione, E., & PELLEGRINO, M. A. (2023) · Foods · doi:10.3390/foods12122286 · Cited by 25
“Examples include amino acid metabolites [235,236], lipids (such as N-acyl amides) [237], derivatives of carbohydrates, including SCFAs, and modifications to bile acids [238].”
Background
Adhesion G-protein coupled receptors: Implications for metabolic function
Olaniru, O. E., & Persaud, S. J. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.02.012 · Cited by 23
“The production of GPR119 agonists by human gastrointestinal bacteria has recently been associated with increased GLP-1 secretion and improved glucose tolerance in mice (Cohen et al., 2017).”
Background
Molecules-mediated bidirectional interactions between microbes and human cells
Wu, S., Bu, X., Chen, D., Wu, X., Wu, H., Caiyin, Q., & Qiao, J. (2025) · npj Biofilms and Microbiomes · doi:10.1038/s41522-025-00657-2 · Cited by 28
“Cohen et al. 53 found that GPR119 agonists analog from commensal microbes regulate metabolic hormones and glucose homeostasis as ef ﬁ - ciently as human ligands.”
Bidirectional GPR119 Agonism Requires Peptide YY and Glucose for Activity in Mouse and Human Colon Mucosa
Tough, I. R., Forbes, S. C., Herzog, H., Jones, R. M., Schwartz, T. W., & Cox, H. M. (2018) · Endocrinology · doi:10.1210/en.2017-03172 · Cited by 23
Causative Microbes in Host-Microbiome Interactions
Britton, G. J., & Faith, J. J. (2021) · Annual Review of Microbiology · doi:10.1146/annurev-micro-041321-042402 · Cited by 20
Personal diet–microbiota interactions and weight loss
Roager, H. M., & Christensen, L. H. (2022) · Proceedings of The Nutrition Society · doi:10.1017/s0029665122000805 · Cited by 23
CDKN1A is a target for phagocytosis-mediated cellular immunotherapy in acute leukemia
Allouch, A., Voisin, L., Zhang, Y., Raza, S. Q., Lécluse, Y., Calvo, J., Selimoglu‐Buet, D., de Botton, S., Louache, F., Pflumio, F., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34548-3 · Cited by 25
Emerging roles of host and microbial bioactive lipids in inflammatory bowel diseases
Kayama, H., & Takeda, K. (2023) · European Journal of Immunology · doi:10.1002/eji.202249866 · Cited by 21
Gut microbiota DPP4-like enzymes are increased in type-2 diabetes and contribute to incretin inactivation
Olivares, M., Hernández-Calderón, P., Cárdenas-Brito, S., Liébana-García, R., Sanz, Y., & Benítez‐Páez, A. (2024) · Genome biology · doi:10.1186/s13059-024-03325-4 · Cited by 23
“Both metabolites activate the GPR132/G2A receptor, which has been implicated in autoimmune disease and atherosclerosis [3, 4].”
Background
At the heart of microbial conversations: endocannabinoids and the microbiome in cardiometabolic risk
Khan, R. N., Maner-Smith, K. M., Owens, J. A., Barbian, M. E., Jones, R. M., & Naudin, C. R. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1911572 · Cited by 24
The role of host molecules in communication with the resident and pathogenic microbiota: A review
White, J. R., Dauros-Singorenko, P., Hong, J., Vanholsbeeck, F., Phillips, A., & Swift, S. (2020) · Medicine in Microecology · doi:10.1016/j.medmic.2020.100005 · Cited by 21
A microbial metabolite synergizes with endogenous serotonin to trigger C. elegans reproductive behavior
Chen, Y.-C., Seyedsayamdost, M. R., & Ringstad, N. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2017918117 · Cited by 23
“Gliotoxin activates egg laying in a manner that requires SER-1/SER-7 GPCRs, and it causes paralysis in a manner that strongly requires the SER-4 GPCR and partly requires the MOD-1 ligand-gated ion channel.”
BackgroundInfluential
Incorporating functional trade-offs into studies of the gut microbiota
Reese, A. T., & Kearney, S. M. (2019) · Current Opinion in Microbiology · doi:10.1016/j.mib.2019.09.003 · Cited by 20
Implication of the Gut Microbiota in Metabolic Inflammation Associated with Nutritional Disorders and Obesity
Rodriguez, J., Olivares, M., & Delzenne, N. M. (2020) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201900481 · Cited by 20
Metabolomics: The Key to Unraveling the Role of the Microbiome in Visceral Pain Neurotransmission
Shute, A., Bihan, D. G., Lewis, I. A., & Nasser, Y. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.917197 · Cited by 21
Etifoxine reverses weight gain and alters the colonic bacterial community in a mouse model of obesity
Ibrahim, K. S., Craft, J. A., Biswas, L., Spencer, J., & Shu, X. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.114151 · Cited by 22
Spp24 is associated with endocytic signalling, lipid metabolism, and discrimination of tissue integrity for ‘leaky-gut’ in inflammatory bowel disease
Wasinger, V. C., Lu, K., Yau, Y. Y., Nash, J., Lee, J., Chang, J., Paramsothy, S., Kaakoush, N. O., Mitchell, H. M., & Leong, R. W. L. (2020) · Scientific Reports · doi:10.1038/s41598-020-69746-w · Cited by 20
Bacterial dysbiosis incites Th17 cell revolt in irradiated gut
Shao, L., Li, M., Zhang, B., & Chang, P. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110674 · Cited by 20
Cannabinoids and Endocannabinoid System Changes in Intestinal Inflammation and Colorectal Cancer
Cherkasova, V., Kovalchuk, O., & Kovalchuk, I. (2021) · Cancers · doi:10.3390/cancers13174353 · Cited by 20
“Changes in the microbiome can lead to increased intestinal wall permeability and inflammation [106].”
BackgroundInfluential
Structures and functions of the gut microbial lipidome
Morozumi, S., Ueda, M., Okahashi, N., & Arita, M. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2021.159110 · Cited by 20
Mutual Links between the Endocannabinoidome and the Gut Microbiome, with Special Reference to Companion Animals: A Nutritional Viewpoint
Moriello, A. S., Marzo, V. D., & Petrosino, S. (2022) · Animals · doi:10.3390/ani12030348 · Cited by 24
MnTE-2-PyP protects fibroblast mitochondria from hyperglycemia and radiation exposure
Chatterjee, A., Sakallioglu, I. T., Murthy, D., Kosmacek, E. A., Singh, P. K., McDonald, J. T., Powers, R., & Oberley‐Deegan, R. E. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102301 · Cited by 20
“Oleoyl tyrosine, an N-acylamide, is involved in lipid signaling [37,38].”
Background
Multiple omics analysis reveals that high fiber diets promote gluconeogenesis and inhibit glycolysis in muscle
Wu, J., Ding, Y., Gong, H., Qi, Y., Sun, H., Liu, Y., Liu, Y., & Qiu, X. (2020) · BMC Genomics · doi:10.1186/s12864-020-07048-1 · Cited by 20
“Moreover, molecular interactions have been reported between the metabolome of the gut microbiota and the human physiology [14, 15].”
Background
Interactions of Gut Endocrine Cells with Epithelium and Neurons
Liddle, R. A. (2018) · Comprehensive physiology · doi:10.1002/cphy.c170044 · Cited by 22
“This panoply of actions was recently illustrated by the discovery that commensal bacteria produce GPR119 agonists that regulate GLP-1 secretion and modulate glucose homeostasis (22).”
The endocannabinoidomes: Pharmacological redundancy and promiscuity, and multi-kingdom variety of sources and molecular targets
Iannotti, F. A., & Marzo, V. D. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100070 · Cited by 23
Proteome of the Triatomine Digestive Tract: From Catalytic to Immune Pathways; Focusing on Annexin Expression
Gumiel, M., de Mattos, D. P., Vieira, C. S., Moraes, C. D. S., Moreira, C. J. D. C., Gonzalez, M. S., Teixeira‐Ferreira, A., Waghabi, M. C., Azambuja, P., & Carels, N. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.589435 · Cited by 18
“Means were compared applying Student’s t-test; *p < 0.05, and ns stands for non-significant. transcription, maintaining gut homeostasis (Schroeder et al., 2008; Marinho et al., 2014; Van der Knaap and Verrijzer, 2016; Cohen et al., 2017).”
MethodInfluential
The human gut microbiome – a new and exciting avenue in cardiovascular drug discovery
Du, Y., Li, X., Su, C., Wang, L., Jiang, J., & Hong, B. (2019) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2019.1638909 · Cited by 20
“synthase gene, exhibiting anti-diabetes phenotypes [130].”
Method
Time-Restricted G-Protein Signaling Pathways via GPR176, Gz, and RGS16 Set the Pace of the Master Circadian Clock in the Suprachiasmatic Nucleus
Nakagawa, S., Pham, K. T. N., Shao, X., & Doi, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21145055 · Cited by 18
Circulating fatty acids and endocannabinoidome-related mediator profiles associated to human longevity
Manca, C., Carta, G., Murru, E., Abolghasemi, A., Ansar, H., Errigo, A., Cani, P. D., Banni, S., & Pes, G. M. (2021) · GeroScience · doi:10.1007/s11357-021-00342-0 · Cited by 18
Characterization of gut dominant microbiota in obese patients with nonalcoholic fatty liver disease
Jin, L.-T., & Xu, M.-Z. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1113643 · Cited by 18
“The binding of lipids encoded by gut flora to G-proteincoupled receptors that control metabolic hormones and glucose homeostasis is one possible mechanism by which gut microbiota may contribute to NAFLD (Cohen et al., 2017).”
Background
The pyruvate–GPR31 axis promotes transepithelial dendrite formation in human intestinal dendritic cells
Oguro-Igashira, E., Murakami, M., Mori, R., Kuwahara, R., Kihara, T., Kohara, M., Fujiwara, M., Motooka, D., Okuzaki, D., Arase, M., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2318767121 · Cited by 17
“…uncharacterized, recent technological advances—including functional metagenomics ( 7 ), bioinformatics in combination with synthetic biology ( 8 ), high - throughput functional profiling approach ( 9 ), and multiplexed bioactivity screening ( 10 )—have led to the identification of many novel…”
The microbiome-gut-brain axis in nutritional neuroscience
Schellekens, H., Ribeiro, G., Cuesta‐Marti, C., & Cryan, J. F. (2022) · Nutritional Neuroscience · doi:10.1080/1028415x.2022.2128007 · Cited by 17
“…reward function [23 – 25] and neuro-cognitive traits [9,26], via pathways that involve the immune system [12,27,28], microbial metabolites [23,25,27,28], neurotransmitters [26,29,30], tryptophan metabolism [30 – 32], G-protein coupled receptors (GPCRs) [23,25,33,34], and epigenetics [35 – 37].”
Lorcaserin and phentermine exert anti-obesity effects with modulation of the gut microbiota
Song, E., Shin, N. R., Jeon, S., Nam, Y., & Kim, H. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.1109651 · Cited by 16
“G protein-coupled receptors (GPRs) are mediators of hostmicrobial interactions (Cohen et al., 2017; Melhem et al., 2019).”
Background
A multi-dimensional view of context-dependent G protein-coupled receptor function
Martí-Solano, M. (2023) · Biochemical Society Transactions · doi:10.1042/bst20210650 · Cited by 17
Microbial metabolites as modulators of host physiology
Joyce, S. A., & Clarke, D. J. (2024) · Advances in microbial physiology/Advances in Microbial Physiology · doi:10.1016/bs.ampbs.2023.12.001 · Cited by 20
Downregulation of GPR183 on infection restricts the early infection and intracellular replication of mycobacterium tuberculosis in macrophage
Tang, J., Shi, Y., Zhan, L., & Qin, C. (2020) · Microbial Pathogenesis · doi:10.1016/j.micpath.2020.104234 · Cited by 17
Adipose tissue–gut microbiome crosstalk in inflammation and thermogenesis
Mauney, E. E., Wibowo, M. C., Tseng, Y., & Kostic, A. D. (2024) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2024.10.004 · Cited by 18
Impact of cannabinoids on cancer outcomes in patients receiving immune checkpoint inhibitor immunotherapy
Vigano, M., Wang, L., As’sadiq, A., Samarani, S., Ahmad, A., & Costiniuk, C. T. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1497829 · Cited by 17
Polyphenols from Foxtail Millet Improve Non-Alcoholic Fatty Liver Disease by Regulating Intestinal Microbiome in Mice
Israr, G., An, Y., Qiao, Q., He, S., & Li, Z. (2024) · Foods · doi:10.3390/foods13111683 · Cited by 16
“Possible mechanistic links between the transformed microbiome and fatty liver are emerging and include the potential for bacterial protein to function as ligands for G protein-coupled receptors [22].”
Background
The diverse roles of sphingolipids in inflammatory bowel disease
Doll, C. L., & Snider, A. J. (2024) · The FASEB Journal · doi:10.1096/fj.202400830r · Cited by 18
“103 Firmicutes and Bacteroidetes are the most prevalent bacteria phyla in the colon and patients suffering from IBD have lower levels of the latter when compared to case-matched controls.”
Key features of the genetic architecture and evolution of host-microbe interactions revealed by high-resolution genetic mapping of the mucosa-associated gut microbiome in hybrid mice
Doms, S., Fokt, H., Rühlemann, M. C., Chung, C. J., Künstner, A., Ibrahim, S. M., Franke, A., Turner, L. M., & Baines, J. F. (2022) · eLife · doi:10.7554/elife.75419 · Cited by 18
Immobilized FhuD2 Siderophore-Binding Protein Enables Purification of Salmycin Sideromycins from Streptomyces violaceus DSM 8286
Rivera, G. S. M., Beamish, C. R., & Wencewicz, T. A. (2018) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.8b00015 · Cited by 16
Polypeptides synthesized by common bacteria in the human gut improve rodent metabolism
Fan, Y., Lyu, L., Vazquez-Uribe, R., Zhang, W., Bongers, M., Koulouktsis, A., Yang, M., Sereikaité, V., Arora, T., Stankevič, E., et al. (2025) · Nature Microbiology · doi:10.1038/s41564-025-02064-x · Cited by 15
“The human microbiome is hypothesized to be a potentially rich but untapped resource for the discovery of novel compounds that may have a regulatory impact on human biology 10,12–14 , 17 .”
Gut Dysbiosis: A New Avenue for Stroke Prevention and Therapeutics
Park, S. Y., Lee, S. P., Kim, D., & Kim, W. J. (2023) · Biomedicines · doi:10.3390/biomedicines11092352 · Cited by 16
“Commensal bacteria produce N-acyl amide, a mimic of human signaling molecules, which controls host glucose metabolism by binding to the G protein-coupled receptor 119 (GPR119) [25].”
Background
The Role of Host Genetics and Intestinal Microbiota and Metabolome as a New Insight into IBD Pathogenesis
Zakerska‐Banaszak, O., Żuraszek-Szymańska, J., Eder, P., Ladziak, K., Słomski, R., & Skrzypczak-Zielińska, M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179589 · Cited by 17
Chemical genetic approaches to dissect microbiota mechanisms in health and disease
Yang, X., & Hang, H. C. (2024) · Science · doi:10.1126/science.ado8548 · Cited by 16
Cannabis and cannabinoid-microbiome interactions in varied clinical contexts: A comprehensive systematic review
Thu, M. S., Campbell, B. J., Hirankarn, N., Nopsopon, T., Ondee, T., Hall, S. R., Jagota, A., Fothergill, J. L., & Pongpirul, K. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117764 · Cited by 16
New voyages to explore the natural product galaxy
Mouncey, N. J., Otani, H., Udwary, D., & Yoshikuni, Y. (2019) · Journal of Industrial Microbiology & Biotechnology · doi:10.1007/s10295-018-02122-w · Cited by 14
“Natural products are a large family of diverse chemical compounds that play important roles in cellular metabolism and in modulating biological systems and their host environments [7, 18, 41] including intra- and intercellular communication [6, 30], host defense [11, 25], nutrient acquisition and pathogenicity [21].”
Background
MASST: A Web-based Basic Mass Spectrometry Search Tool for Molecules to Search Public DataPreprint
Wang, M., Jarmusch, A. K., Vargas, F., Aksenov, A. A., Gauglitz, J. M., Weldon, K. C., Petras, D., Silva, R., Quinn, R., Melnik, A. V., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/591016 · Cited by 14
An overview of basic pathophysiological interactions between gut bacteria and their host
Simonson, M., Simonson, T., & Nobécourt, E. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1565609 · Cited by 14
Unraveling function and diversity of bacterial lectins in the human microbiome
Cohen, L. J., Han, S. M., Lau, P., Guisado, D., Liang, Y., Nakashige, T. G., Ali, T. A., Chiang, D., Rahman, A. H., & Brady, S. F. (2022) · Nature Communications · doi:10.1038/s41467-022-29949-3 · Cited by 13
N ‐Acyl Amides from Neisseria meningitidis and Their Role in Sphingosine Receptor Signaling
Cho, W., York, A. G., Wang, R., Wyche, T. P., Piizzi, G., Flavell, R. A., & Crawford, J. M. (2022) · ChemBioChem · doi:10.1002/cbic.202200490 · Cited by 13
Understanding the gut microbiota by considering human evolution: a story of fire, cereals, cooking, molecular ingenuity, and functional cooperation
Tannock, G. W. (2023) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00127-22 · Cited by 15
Untargeted metabolomics unravels distinct gut microbial metabolites derived from plant-based and animal-origin proteins using in vitro modeling
Izquierdo-Sandoval, D., Duan, X., Fryganas, C., Portolés, T., Sancho, J. V., & Rubert, J. (2024) · Food Chemistry · doi:10.1016/j.foodchem.2024.140161 · Cited by 13
Staphylococcus aureus lipid factors modulate melanoma cell clustering and invasion
Giese, M. A., Ramakrishnan, G., Steenberge, L. H., Dovan, J. X., Sauer, J., & Anna Huttenlocher, A. (2024) · Disease Models & Mechanisms · doi:10.1242/dmm.050770 · Cited by 13
Hyperlipidemias and Obesity
Thiriet, M. (2018) · Biomathematical and biomechanical modeling of the circulatory and ventilatory systems · doi:10.1007/978-3-319-89315-0_5 · Cited by 14
Vagal interoception of microbial metabolites from the small intestinal lumenPreprint
Jameson, K. G., Kazmi, S. A., Son, C., Mazdeyasnan, D., Leshan, E., Vuong, H. E., Paramo, J., Lopez-Romero, A., Yang, L., Schweizer, F. E., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.12.18.572257 · Cited by 13
Lactiplantibacillus plantarum strengthens the intestinal barrier: involvement of the endocannabinoidome
Allam‐Ndoul, B., Pulido-Mateos, E. C., Bégin, F., St‐Arnaud, G., Tinoco-Mar, B. A., Mayer, T., Dumais, E., Flamand, N., Raymond, F., Roy, D., et al. (2025) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00142.2024 · Cited by 12
Weak Microbial Metabolites: a Treasure Trove for Using Biomimicry to Discover and Optimize Drugs
Dvořák, Z., Klapholz, M., Burris, T. P., Willing, B. P., Gioiello, A., Pellicciari, R., Galli, F., March, J. C., O’Keefe, S. J., Sartor, R. B., et al. (2020) · Molecular Pharmacology · doi:10.1124/molpharm.120.000035 · Cited by 12
“Similar examples are shown by Cohen et al. (2017), whereby a microbiome-synthetic gene-therapy approach is applied toward GPR119-targeted therapy, given that human microbiota produce N-acyl amides that mimic human GPR119 ligands.”
Background
A Genomics-Based Semirational Approach for Expanding the Postbiotic Potential of Collagen Peptides Using Lactobacillaceae
Lee, J., Hwang, H. W., Jin, H., Lee, J.-E., Kang, N. J., & Lee, D. (2022) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.2c01251 · Cited by 13
Contribution of gut microbiota–host cooperation to drug efficacy
Delzenne, N. M., & Bindels, L. B. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.170 · Cited by 12
Angiotensin (1–7) Expressing Probiotic as a Potential Treatment for Dementia
Hernandez, A. R., Banerjee, A., Carter, C. S., & Buford, T. W. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.629164 · Cited by 12
“Once thought to contribute primarily to allergic and/or inflammatory intestinal disorders, the gut microbiota are now known to communicate with organs far from the intestine (Belkaid and Naik, 2013; Cohen et al., 2017).”
Meta‐Omics‐ and Metabolic Modeling‐Assisted Deciphering of Human Microbiota Metabolism
Sieow, B. F., Nurminen, T. J., Ling, H., & Chang, M. W. (2019) · Biotechnology Journal · doi:10.1002/biot.201800445 · Cited by 12
Role of the Endocannabinoidome in Human and Mouse Atherosclerosis
Piscitelli, F., & Silvestri, C. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666190826162735 · Cited by 13
The Endocannabinoids-Microbiota Partnership in Gut-Brain Axis Homeostasis: Implications for Autism Spectrum Disorders
Coccurello, R., Marrone, M. C., & Maccarrone, M. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.869606 · Cited by 12
“, 2015), and N-oleoylserinol that is an agonist of the eCB receptor GPR119 (Cohen et al., 2017).”
BackgroundInfluential
Insights into a novel chrysanthemum-coix seed beverage prepared by enzymatic hydrolysis: Chemical profile, sensory quality, and functional property
Rao, H., Lin, L., & Zhao, M. (2023) · Food Bioscience · doi:10.1016/j.fbio.2023.102490 · Cited by 11
Potential for host-symbiont communication via neurotransmitters and neuromodulators in an aneural animal, the marine sponge Amphimedon queenslandica
Xiang, X., Gomez, A. A. V., Blomberg, S. P., Yuan, H., Degnan, B. M., & Degnan, B. M. (2023) · Frontiers in Neural Circuits · doi:10.3389/fncir.2023.1250694 · Cited by 11
“These symbiont signals appear to act largely through the host’s G-protein coupled receptors (GPCRs) (Cohen et al., 2017; Husted et al., 2017; Chen et al., 2019; Colosimo et al., 2019; Pandey et al., 2019).”
Background
Exploring the versatile roles of the endocannabinoid system and phytocannabinoids in modulating bacterial infections
Barker, H., & Ferraro, M. J. (2024) · Infection and Immunity · doi:10.1128/iai.00020-24 · Cited by 11
“The gastrointestinal receptor GPR119, which is engaged in energy homeostasis and metabolic processes, emerges as a nexus for both eCBs and microbial byproducts within the host’s microbiome (170).”
Background
Lipids from gut microbiota: pursuing a personalized treatment
Carneiro, P. V., Montenegro, N. D. A., Lana, A. J., Amato, A. A., & Santos, G. M. (2022) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2022.06.001 · Cited by 12
Recent progress on signalling molecules of coral-associated microorganisms
Tang, K., Wang, Y., & Wang, X. (2019) · Science China Earth Sciences · doi:10.1007/s11430-018-9332-1 · Cited by 11
Designing bugs as drugs: exploiting the gut microbiome
Lamousé-Smith, E. S. N., Kelly, D., & de Cremoux, I. (2020) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00381.2019 · Cited by 11
N-acyl glycines produced by commensal bacteria potentiate GLP-1 secretion as GPCR ligands
Drzazga, A. K., Bernat, P., Nowak, A., Szustak, M., Korkus, E., Gendaszewska‐Darmach, E., & Koziołkiewicz, M. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117467 · Cited by 11
Ornithine lipids from Akkermansia muciniphila are dynamically modulated in colitis and shape macrophage inflammatory responses
Selmi, H., Walker, A., Balas, L., Lucio, M., Klotz, M., Jeridi, A., Burrichter, A. G., Conti, D. E., Chaffringeon, L., Beinsteiner, B., et al. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2601376 · Cited by 10
“50 Treatment with synthetic 3-OH-C16:0 reduced INOS expression in LPS-stimulated macrophages, suggesting a potential regulatory effect of OL-derived metabolites.”
Novel Anticancer Strategy by Targeting the Gut Microbial Neurotransmitter Signaling to Overcome Immunotherapy Resistance
Leung, E. L., Huang, J., Zhang, J., Zhang, J., Wang, M., Zhu, Y., Meng, Z., Yu, H., Neher, E., Ma, L., et al. (2022) · Antioxidants and Redox Signaling · doi:10.1089/ars.2021.0243 · Cited by 11
“To further deﬁne the role of microbiota-encoded effectors in host–microbial interactions, synthetic biology (such as CRISPR-Cas9 genome editing or in situ microbiome engineering) and bioinformatic analysis of gut microbiome sequencing data were of great signiﬁcance (Cohen et al, 2017).”
Probiotic fermentation affects the chemical characteristics of coix seed-chrysanthemum beverage: Regulatory role in sensory and nutritional qualities
Rao, H., Lin, L., & Zhao, M. (2024) · Food Bioscience · doi:10.1016/j.fbio.2024.103629 · Cited by 10
The Human Fecal Endocannabinoidome Mediator Profile Is Mainly Defined by the Fecal Microbiota and Diet
Castonguay-Paradis, S., Parent, L., St‐Arnaud, G., Perron, J., Dumais, É., Flamand, N., Raymond, F., Marzo, V. D., & Veilleux, A. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae586 · Cited by 10
Broad range lipidomics and metabolomics coupled with 16S rRNA sequencing to reveal the mechanisms of Huangkui Capsule against cisplatin-induced nephrotoxicity
Liao, J.-C., Xiang, J., Gui, W., Luo, H.-Z., You, Q., He, Q., Lu, M., Yang, S., Wang, Q., Zou, J., et al. (2024) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2024.119197 · Cited by 10

Authors: Cohen, L. J., Esterhazy, D., Kim, S.-H., Lemetre, C., Aguilar, R. R., Gordon, E. A., Pickard, A. J., Cross, J. R., Emiliano, A. B., Han, S. M., Chu, J., Vila-Farres, X., Kaplitt, J., Rogoz, A., Calle, P. Y., Hunter, C., Bitok, J. K., & Brady, S. F.
Affiliations: Rockefeller University (US)
Memorial Sloan Kettering Cancer Center (US)
Corresponding author: Brady, Sean F.
ORCID: Cohen, Louis J.
Kim, Seong-Hwan
Aguilar, Rhiannon R.
Gordon, Emma A.
Pickard, Amanda J.
Cross, Justin R.
Emiliano, Ana B.
Brady, Sean F.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2017-08-30
Volume: 549
Issue: 7670
Pages: 48-53
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature23874
PMC: PMC5777231
OpenAlex: W2753100975
Cited by: 500
References: 45
Citations by year: 2026: 44 · 2025: 47 · 2024: 60 · 2023: 53 · 2022: 52 · 2021: 44 · 2020: 64 · 2019: 62 · 2018: 55 · 2017: 18
FWCI: 22.22
Type: journal article
Language: en
Update notices: erratum (2018-04-05)
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: Crohn's and Colitis Foundation (370629)
National Institute of General Medical Sciences (U01GM110714, R35GM122559)
National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007792, K08DK109287)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Microbial Natural Products and Biosynthesis
Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords: commensal bacteria, G protein-coupled receptors, GPR119, gut microbiota metabolites, glucose homeostasis, metabolic hormones, gastrointestinal tract physiology
MeSH terms: Biological Mimicry, Gastrointestinal Microbiome, Amides, Animals, Bacteria, Blood Glucose, Female, Homeostasis, Humans, Ligands, Male, Symbiosis, Signal Transduction, Gastrointestinal Tract, Receptors, G-Protein-Coupled, Mice, HEK293 Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Commensal bacteria make GPCR ligands that mimic human signalling molecules

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks